Document Detail


CD26/dipeptidylpeptidase IV-targeted therapy of acute lung rejection in rats.
MedLine Citation:
PMID:  16962474     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: CD26 is a T-cell co-stimulator, and interacts with adenosine deaminase, human immunodeficiency virus (HIV) Tat-1 protein and extracellular matrix. It possesses dipeptidylpeptidase IV (DPP IV) catalytic activity, which is linked to its co-stimulatory efficacy. We investigated the effect of specific DPP IV systemic activity inhibition on acute pulmonary rejection. METHODS: Rat single-lung transplantation (Tx) was performed (LBNF1/LEW donor/recipient) in two groups (n = 12). Group I (n = 6) received daily treatment with a Pro-Pro-diphenylphosphonate derivative (AB197), and Group II served as an untreated control. At Day 5 post-Tx, ventilatory parameters, cytotoxicity and mixed lymphocyte reaction were analyzed and staining for ISHLT rejection grade and proliferating cell nuclear antigen (PCNA) was performed. RESULTS: Treatment with AB192 abrogated acute rejection and preserved pulmonary function up to Day 5 post-Tx for PO2 (Group II: 24.9 +/- 6.9 mm Hg; Group I: 149.5 +/- 24.3 mm Hg; p < 0.001), PCO2 (Group II: 53.3 +/- 13.6 mm Hg; Group I: 39.0 +/- 9.8 mm Hg; p < 0.05) and peak airway pressure (Group II: 50.7 +/- 17.2 mm Hg; Group I: 20.2 +/- 10.0 mm Hg; p < 0.01). Controls showed moderate/severe rejection (ISHLT Grade A2 or 3), grafts from inhibited hosts revealed no/mild rejection (Grade A0 to 2: Group II: 2.8 +/- 0.3; Group I: 1.25 +/- 1.0; p < 0.005). Proliferating cell nuclear antigen (PCNA) staining of rejection-associated cellular infiltrates showed a significant reduction in positivity in perivascular infiltrates (34 +/- 11.5%; p < 0.05) and bronchial surface epithelium (31.7 +/- 10.6%; p < 0.05) in Group I vs Group II (55.9 +/- 8.4% and 57.2 +/- 4.5%). CONCLUSIONS: Irreversible enzymatic inhibition of DPP IV has been shown to abrogate acute pulmonary rejection, maintain pulmonary function, and preserve histomorphologic architecture. These results extend earlier findings and illustrate the role of CD26/DPP IV in alloantigen-mediated immune responses.
Authors:
Florian Johannes Jung; Lin Yang; Ingrid De Meester; Koen Augustyns; Markus Cardell; Sven Hillinger; Peter Vogt; Didier Lardinois; Simon Scharpé; Walter Weder; Stephan Korom
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-17
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  25     ISSN:  1557-3117     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-11     Completed Date:  2006-10-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1109-16     Citation Subset:  IM    
Affiliation:
Department of Thoracic Surgery, University Hospital Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD26 / blood,  physiology*
Cell Proliferation / drug effects
Dipeptides / pharmacology
Enzyme Inhibitors / pharmacology,  therapeutic use*
Graft Rejection / drug therapy*,  enzymology*,  prevention & control
Isoantigens / physiology
Lung / enzymology,  pathology,  physiopathology
Lung Transplantation / immunology,  pathology,  physiology*
Male
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
0/AB197 compound; 0/Dipeptides; 0/Enzyme Inhibitors; 0/Isoantigens; EC 3.4.14.5/Antigens, CD26

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